We study the regulation of amino acid biosynthetic genes in budding yeast as a means of dissecting mechanisms of transcriptional control of gene expression. Transcription of these genes is coordinately induced by the activator Gcn4 during amino acid limitation--the general amino acid control (GAAC)--owing to accumulation of Gcn4 in starved cells. We showed previously that transcriptional activation by Gcn4 is enhanced by its recruitment of coactivator complexes Mediator, SAGA, SWI/SNF, and RSC, which in turn stimulate recruitment of general transcription factors and RNA Polymerase II (Pol II) to the promoter to stimulate preinitiation complex (PIC) assembly. We further demonstrated that SAGA is recruited co-transcriptionally to coding sequences (CDS) by association with the Ser5-phosphorylated C-terminal domain (CTD) of Pol II, and that the histone acetyltransferase (HAT) subunit of SAGA (Gcn5) promotes increased histone acetylation, histone eviction, Pol II processivity, and histone H3-Lys4 methylation within CDS. We showed that histone H4 HAT complex, NuA4, is also recruited co-transcriptionally via Ser5 phosphorylation of the Pol II CTD by cyclin-dependent kinase (CDK) Cdk7/Kin28, and that NuA4 association with nucleosomes also depends on H3 methylation, presumably due to chromodomains and a PHD finger in NuA4 subunits. We obtained evidence that HAT activities of NuA4 and SAGA cooperate to enhance co-transcriptional recruitment of nucleosome remodeling complex RSC, promote histone eviction from transcribed CDS, and stimulate Pol II elongation. We subsequently extended the two-stage recruitment mechanism elucidated for NuA4, via Ser5P and methylated histones, to include histone deacetylase complexes (HDACs) Rpd3C(S) and Set3C. Our results revealed that, whereas interaction with methylated H3 is required for Rpd3C(S) and Set3C deacetylation activities, their co-transcriptional recruitment is stimulated by the phospho-CTD. We further demonstrated that the HDAs Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating nucleosomes and in limiting co-transcriptional nucleosome eviction, and provided evidence that histone acetylation is a key determinant of co-transcriptional nucleosome eviction. Our group also demonstrated that recruitment of conserved transcription elongation factor Paf1C by Pol II is stimulated by elongation factor DSIF (comprised of Spt4 and Spt5) and the CDKs Cdk7/Kin28 and Cdk9/Bur1. We showed that Ser5-CTD phosphorylation by Kin28 enhances recruitment of Bur1, which promotes Ser2-CTD phosphorylation near promoters in addition to phosphorylating C-terminal repeats (CTRs) of Spt5. We established that Kin28 and Bur1 collaborate to generate Ser2-,Ser5-diphosphorylated CTD repeats that, together with Spt5 phospho-CTRs, recruit Paf1C via multiple phospho-interaction domains in different Paf1C subunits. More recently, we elucidated the mechanism whereby accumulation of a toxic biosynthetic intermediate attenuates GAAC. Having found that transcriptional activation by Gcn4 is impaired in mutants lacking threonine biosynthetic enzyme HOM6, we determined that accumulation of the Hom6 substrate, beta-aspartate semialdehyde, accelerates the already rapid degradation of Gcn4, dependent on its phosphorylation by the CDKs Srb10 and Pho85. By determining the specific activities of promoter-bound Gcn4 molecules rescued from degradation in srb10 versus pho85 mutants, we uncovered a division of labor between these kinases wherein Srb10 primarily targets inactive Gcn4 molecules while Pho85 clears functional Gcn4 species. NuA4 links methylation of histone H3 lysines 4 and 36 to acetylation of histones H4 and H3 Cotranscriptional methylation of histone H3 lysines 4 and 36 by Set1 and Set2, respectively, stimulates interactions between nucleosomes and HDACs that evoke histone deacetylation and suppresses transcription from cryptic promoters. Subunits of HAT complex NuA4 also contain histone-interaction domains (CHDs and PHD fingers), and we showed previously that loss of all H3K4 and H3K36 methylation in a set1set2 double mutant reduces interaction between native nucleosomes and NuA4. We have now provided evidence that NuA4 preferentially binds H3 tails mono- and dimethylated on H3K4 and di- and trimethylated on H3K36an H3 methylation pattern distinct from that recognized by the Rpd3C(S) and Set3C HDACs. Loss of H3 methylation in set1 or set2 mutants reduces NuA4 interaction with nucleosomes in vitro and in vivo, and decreases NuA4 occupancy at particular genes. Furthermore, NuA4 acetylation of H4 tail lysines stimulates SAGA interaction with nucleosomes and its recruitment and attendant acetylation of H3 in vivo. Thus, H3 methylation exerts opposing effects of enhancing nucleosome acetylation by NuA4 and SAGA while stimulating nucleosome deacetylation by HDACs to maintain the proper level of histone acetylation in transcribed genes. Moreover, recruitment of one HAT complex (NuA4) was found to enhance that of another (SAGA) with complementary histone substrate specificity. Analysis of factors mediating nucleosome disassembly at Gcn4 target gene promoters in vivo. A key unsolved aspect of transcriptional activation by Gcn4 is how it mediates the eviction of nucleosomes that occlude promoter DNA sequences and block access by GTFs and Pol II. Indeed, the mechanism of this key step of gene activation, and the impact of defective nucleosome eviction on transcription, are not fully understood for any yeast genes. Previous studies implicated certain histone chaperones, chromatin remodelers or histone acetyltransferases in the remodeling or eviction of nucleosomes from the promoters of certain yeast genes, but it was unclear whether these co-factors function broadly in nucleosome eviction, as co-factor requirements at most yeast promoters are unknown. Eviction of promoter nucleosomes is considered to be rate-limiting for transcriptional activation, but the consequences of impaired nucleosome eviction on transcription have not been analyzed genome-wide. We addressed these questions by analyzing histone H3 eviction for the hundreds of genes in the Gcn4 transcriptome on induction of Gcn4 in a large panel of mutants lacking one or more co-factors implicated at particular yeast genes. By conventional chromatin immunoprecipitation analysis (ChIP) of four canonical Gcn4 target genes, ARG1, HIS4, ARG4, and CPA2, we excluded a requirement for several co-factors implicated previously at other genes (eg. Asf1, Nap1, RSC) and implicated the remodeler SWI/SNF (Snf2), HAT Gcn5, and Hsp70 co-chaperone Ydj1 in nucleosome eviction at these Gcn4 target genes. Expanding our analysis genome-wide by H3 ChIP-Seq, we found that Snf2, Gcn5 and Ydj1 collaborate in evicting H3 from the -1 and +1 promoter nucleosomes, and intervening nucleosome-depleted region (NDR) at a large fraction of the Gcn4 transcriptome. These 3 cofactors were found to function similarly at virtually all yeast promoters. Surprisingly, however, defective H3 eviction in co-factor mutants was coupled with reduced transcription (Pol II densities measured by Rpb3 ChIP-Seq) for only a subset of genes, which included the induced Gcn4 transcriptome and the most highly expressed subset of constitutively expressed yeast genes. In fact, the most weakly expressed genes displayed an increase in transcription relative to other genes in response to global attenuation of nucleosome eviction. Thus, we established that steady-state eviction of promoter nucleosomes is required for maximal transcription of highly expressed genes, and that Gcn5, Snf2, and Ydj1 function broadly in this step of gene activation, but discovered unexpectedly that some other aspect of transcriptional activation is more generally rate-limiting for transcription of most genes in amino acid-deprived yeast.